How should you be measuring and reporting urine albumin?

The Laboratory Working Group (LWG) of the National Kidney Disease Education Program and the Working Group for Standardization of Albumin in Urine (WG-SAU) of the IFCC have made recommendations on best practices for measuring and reporting urine albumin (UA).The initial recommendations (1) have been followed up with further clarifications all summarized here. The term urine albumin should be used for the name of the test because “microalbumin” is not a molecule but rather refers to a condition of a small pathological amount of albumin in urine.Urine albumin should not be reported only as a concentration, e.g. mg/L, but the report should always also include the albumin to creatinine ratio (ACR) in mg/g or mg/mmole. Ideally only one unit would be used globally; but the same unit should be used within a country or geographical region.The ACR is highly correlated with the albumin excretion rate (AER) which is a primary marker for evaluation of kidney function and assessment of kidney damage. In contrast, the albumin concentration without normalization for creatinine is influenced by hydration and poorly correlates with the AER.

The preferred urine specimen for measurement of the ACR is a first morning void because within individual biological variability of a first morning void specimen is equivalent to that of a 24 hour urine AER. A 24 hour collection is not required for interpretation of the ACR. Because a first morning void is inconvenient for typical office visits, a random urine collection is acceptable to screen for elevated UA. A random urine has larger biological variability and poorer correlation with AER, therefore use of a random urine specimen will cause increased false positive results. Consequently, an elevated random urine ACR should be followed up with a first morning void to confirm persistent elevation (2). Freshly collected urine can be stored up to 1 week at 4-8 °C before measurement. If longer storage is needed, the urine should be frozen at -70 °C or lower.

High UA and ACR values are important for following progression and response to treatment of kidney disease.UA values above the analytical measuring range should be diluted to reduce the concentration to a measurable value and a quantitative value reported for the concentration in the urine (3).If the manufacturer of a measurement procedure does not provide a recommended diluent or a dilution protocol, the laboratory should establish and validate a dilution protocol.

The Kidney Disease Improving Global Outcomes recommendations (4) and most national recommendations use fixed decision values for the ACR to classify kidney disease severity.Urine creatinine results are reasonably well standardized as a consequence of the work to standardize serum/plasma/blood creatinine measurements. UA results are not standardized among different clinical laboratory measurement procedures (5).Consequently, it is likely that incorrect classifications occur for ACR values near the clinical decision values.At this time, an individual laboratory cannot address the standardization issue. The LWG and WG-SAU are collaborating with metrology institutes, academic centers and in-vitro diagnostics manufacturers to develop higher order reference materials and reference measurement procedures to enable standardization of UA measurement procedures (6, 7).

We encourage laboratories to adopt the best practice recommendations described here for measuring and reporting UA.Further improvement will be achieved when the UA standardization program is implemented in the next few years.

References

1. Miller WG, Bruns DE, Hortin GL, Sandberg S, Aakre KM, McQueen MJ, et al. Current Issues in Measurement and Reporting of Urinary Albumin Excretion. Clin Chem 2009;55:24-38.
2. Saydah SH, Pavkov ME, Zhang C, Lacher DA, Eberhardt MS, Burrows NR, et al. Albuminuria prevalence in first morning void compared with previous random urine from adults in the National Health and Nutrition Examination Survey, 2009-2010. Clin Chem 2013;59:675-83.
3. Miller WG, Bachmann LM, Fleming JK, Delanghe JR, Parsa A, Narva AS. Recommendations for Reporting Low and High Values for Urine Albumin and Total Protein. Clin Chem; ahead of print at DOI: 10.1373/clinchem.2018.297861.
4. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3:1–150.
5. Bachmann LM, Nilsson G, Bruns DE, McQueen MJ, Lieske JC, Zakowski JJ, Miller WG. State of the art for measurement of urine albumin: comparison of routine measurement procedures to isotope dilution tandem mass spectrometry. Clin Chem. 2014;60: 471-80.
6. Miller WG, Seegmiller JC, Lieske JC, Narva AS, Bachmann LM. Standardization of Urine Albumin Measurements:Status and Performance Goals. J Applied Lab Med 2017;2:423-9.
7. Seegmiller JC, Miller WG, Bachmann LM. Moving towards standardization of urine albumin measurements. eJIFCC 2017;28:258-67.